Article
Biology
Kelly Z. Young, Carolina Rojas Ramirez, Simon G. Keep, John R. Gatti, Soo Jung Lee, Xiaojie Zhang, Magdalena I. Ivanova, Brandon T. Ruotolo, Michael M. Wang
Summary: Specific cysteine residue alterations and quaternary structures are induced by CADASIL mutations in NOTCH3, leading to oligomeric states, altered disulphide bonding, increased free thiols, and reduced protein stability.
COMMUNICATIONS BIOLOGY
(2022)
Article
Neurosciences
Wang Ni, Yi Zhang, Liang Zhang, Juan-Juan Xie, Hong-Fu Li, Zhi-Ying Wu
Summary: This study identified new NOTCH3 mutations and known variants in 1401 CADASIL pedigrees from Asian and Caucasian populations. Asians were more prone to develop TIA or ischemic stroke and cognitive impairment, while Caucasians had a higher tendency for migraine and psychiatric disturbance. The findings contribute to a better understanding of the clinical variability and genetic heterogeneity of CADASIL.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Article
Clinical Neurology
Gido Gravesteijn, Remco J. Hack, Aat A. Mulder, Minne N. Cerfontaine, Remco van Doorn, Ingrid M. Hegeman, Carolina R. Jost, Julie W. Rutten, Saskia A. J. Lesnik Oberstein
Summary: CADASIL patients with an EGFr 7-34 variant have significantly less vascular NOTCH3 aggregation than patients with an EGFr 1-6 variant. This may be one of the factors underlying the difference in disease severity between NOTCH3(cys) EGFr 7-34 and EGFr 1-6 variants.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Article
Clinical Neurology
Remco J. Hack, Gido Gravesteijn, Minne N. Cerfontaine, Mark A. Santcroos, Laura Gatti, Anna Kopczak, Anna Bersano, Marco Duering, Julie W. Rutten, Saskia A. J. Lesnik Oberstein
Summary: A novel three-tiered risk classification for NOTCH3 variants associated with CADASIL disease prediction has been identified in this study.
Article
Biochemistry & Molecular Biology
Shodai Suzuki, Satoshi Hiura, Taiki Mashiko, Takemi Matsumoto, Motoyuki Itoh
Summary: CADASIL is a genetic small vessel disease characterized by NOTCH3 mutation and abnormal aggregation of NOTCH3 mutant proteins. SD NOTCH3 mutants may be more likely to accumulate than SA NOTCH3 mutants upon interaction with JAG1, and LFNG may play an important role in promoting the aggregation of SA NOTCH3 mutants.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Daniel V. Oliveira, Julia Svensson, Xueying Zhong, Henrik Biverstal, Gefei Chen, Helena Karlstrom
Summary: CADASIL is a familial form of stroke caused by mutations in the NOTCH3 gene, resulting in neuronal death. This study suggests that the BRICHOS domain has anti-aggregating properties on the mutated protein, which could be a potential treatment for CADASIL.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Medicine, General & Internal
Yuxiang Qi, Hairong Li, Ling Yu
Summary: This article reports a case of CADASIL with a heterozygous mutation in the NOTCH3 gene. Despite not exhibiting the typical clinical findings of CADASIL, the patient's cerebral magnetic resonance imaging was consistent with the characteristic findings of CADASIL. This case reminds us that mutations caused by different mutation sites present different clinical symptoms.
Article
Genetics & Heredity
Yacen Hu, Qiying Sun, Yafang Zhou, Fang Yi, Haiyun Tang, Lingyan Yao, Yun Tian, Nina Xie, Mengchuan Luo, Zhiqin Wang, Xinxin Liao, Hongwei Xu, Lin Zhou
Summary: CADASIL is a cerebral small vessel disease caused by mutations in the NOTCH3 gene. The study found that patients carrying cysteine-sparing pathogenic variants showed later symptom onset and milder temporal lobe involvement than patients carrying cysteine-affecting pathogenic variants.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
Juyi Li, Tao Luo, Xiufang Wang, Mengjie Wang, Tao Zheng, Xiao Dang, Aiping Deng, Youzhi Zhang, Sheng Ding, Ping Jing, Lin Zhu
Summary: A known CADASIL-causing mutation NOTCH3 (c.397C > T, p.Arg133Cys) was identified in a Chinese family. The clinical manifestations of mutation carriers in this family are highly heterogeneous, which is likely a common feature for the etiology of different mutations in CADASIL. Molecular genetic analyses are critical for accurate diagnosis and genetic counseling for CADASIL.
FRONTIERS IN GENETICS
(2022)
Article
Clinical Neurology
Jun Takei, Yujiro Higuchi, Masahiro Ando, Akiko Yoshimura, Jun-Hui Yuan, Natsumi Fujisaki, Takashi Tokashiki, Naomi Kanzato, Manabu Jonosono, Takeshi Sueyoshi, Naoaki Kanda, Hideki Matsuoka, Ryuichi Okubo, Masahito Suehara, Eiji Matsuura, Hiroshi Takashima
Summary: This study aimed to identify the genetic and clinical features of CADASIL in Japan. Genetic and clinical analyses were performed on 32 patients with pathogenic mutations in the NOTCH3 gene. It was found that the R75P mutation was associated with the development of CADASIL and the presence of cerebral microbleeds, suggesting it as a potentially characteristic imaging feature.
FRONTIERS IN NEUROLOGY
(2023)
Article
Medicine, Research & Experimental
Daniel Oliveira, Kirsten G. Coupland, Wenchao Shao, Shaobo Jin, Francesca Del Gaudio, Sailan Wang, Rhys Fox, Julie W. Rutten, Johan Sandin, Henrik Zetterberg, Johan Lundkvist, Saskia Aj Lesnik Oberstein, Urban Lendahl, Helena Karlstrom
Summary: In this study, a novel active immunization therapy specifically targeting CADASIL-like aggregated NOTCH3 extracellular domain (ECD) was developed and tested on CADASIL mice. The therapy successfully reduced NOTCH3 deposition around brain capillaries, increased microglia activation, and lowered serum levels of NOTCH3 ECD.
EMBO MOLECULAR MEDICINE
(2023)
Article
Medicine, Research & Experimental
Chunjing Lin, Ziyang Huang, Riyong Zhou, Ying Zhou, Yangping Shentu, Kang Yu, Yu Zhang
Summary: This study investigated the effects of Notch3 mutants on various cell lines, showing that the mutants had different impacts on cell behavior in different cell types. The findings shed light on the underlying mechanisms of CADASIL.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Neurosciences
Lina Guo, Bin Jiao, Xinxin Liao, Xuewen Xiao, Weiwei Zhang, Zhenhua Yuan, Xixi Liu, Lu Zhou, Xin Wang, Yuan Zhu, Qijie Yang, Junling Wang, Beisha Tang, Lu Shen
Summary: This study identified multiple pathogenic variants of NOTCH3, confirming its pathological role in SVaD, but found no association with AD.
CNS NEUROSCIENCE & THERAPEUTICS
(2021)
Article
Multidisciplinary Sciences
Xiaojie Zhang, Soo Jung Lee, Michael M. Wang
Summary: In CADASIL patients, NOTCH3 protein is cleaved at a high level at Asp121, while control vessels harbor only a small amount of cleaved NOTCH3. Similar to other neurodegenerative conditions, chronic brain vascular disease features proteolysis of pathological proteins at multiple sites, which may generate small pathological peptides.
SCIENTIFIC REPORTS
(2021)
Article
Medical Laboratory Technology
Jiahui Liu, Qiaoyu Zhang, Qi Wang, Siyu Luan, Xiang Dong, Hua Cao, Dingbo Tao, Huijie Dong, Xiaofei Ji
Summary: A heterozygous deletion-insertion mutation in exon 4 of the NOTCH3 gene was identified in a CADASIL patient through whole-exome sequencing. This discovery provides a significant theoretical basis for specific gene-based diagnosis and treatment of CADASIL.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2021)
Article
Surgery
Samuel Jang, Meagan Mandabach, Zviadi Aburjania, Courtney J. Balentine, Herbert Chen
JOURNAL OF SURGICAL RESEARCH
(2018)
Article
Oncology
Jong Jin Hyun, J. Bart Rose, Adnan A. Alseidi, Thomas R. Biehl, Scott Helton, David L. Coy, Richard A. Kozarek, Flavio G. Rocha
JOURNAL OF SURGICAL ONCOLOGY
(2019)
Editorial Material
Surgery
J. Bart Rose
SURGICAL CLINICS OF NORTH AMERICA
(2019)
Article
Surgery
Brendon Herring, Jason Whitt, Tolulope Aweda, Jianfa Ou, Rachael Guenter, Suzanne Lapi, Joel Berry, Herbert Chen, Xiaoguang Liu, J. Bart Rose, Renata Jaskula-Sztul
Review
Medicine, General & Internal
Bin Ren, J. Bart Rose, Yehe Liu, Renata Jaskular-Sztul, Carlo Contreras, Adam Beck, Herbert Chen
JOURNAL OF CLINICAL MEDICINE
(2019)
Editorial Material
Surgery
J. Bart Rose
AMERICAN JOURNAL OF SURGERY
(2020)
Article
Oncology
J. Bart Rose, Alicia M. Edwards, Flavio G. Rocha, Carolyn Clark, Adnan A. Alseidi, Thomas R. Biehl, Bruce S. Lin, Vincent J. Picozzi, W. Scott Helton
Review
Oncology
Seifeldin Awad, Ahmad M. Alkashash, Magi Amin, Samantha J. Baker, J. Bart Rose
FRONTIERS IN ONCOLOGY
(2020)
Review
Oncology
Francesco Giovinazzo, Fiammetta Soggiu, Jin-Young Jang, Eva Versteijne, Geertjan van Tienhoven, Casper H. van Eijck, Youngmin Han, Seong Ho Choi, Chang Moo Kang, Mark Zalupski, Hasham Ahmad, Sarah Yentz, Scott Helton, J. Bart Rose, Chie Takishita, Yuichi Nagakawa, Mohammad Abu Hilal
FRONTIERS IN ONCOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Zviadi Aburjania, Jason D. Whitt, Samuel Jang, Dwayaja H. Nadkarni, Herbert Chen, J. Bart Rose, Sadanandan E. Velu, Renata Jaskula-Sztul
Article
Oncology
Tyler R. McCaw, Evelyn Inga, Herbert Chen, Renata Jaskula-Sztul, Vikas Dudeja, James A. Bibb, Bin Ren, J. Bart Rose
Summary: Gamma secretase inhibitors (GSIs), originally developed as Alzheimer's therapies, have been repurposed as anticancer agents due to their ability to inhibit Notch receptor cleavage. Despite showing promise in preclinical models, GSIs have not demonstrated significant clinical benefit in most solid tumors. Further research is needed to address limitations in understanding GSI mechanisms and improve their efficacy in cancer treatment.
Article
Surgery
Juliet S. Okoroh, Lauren Weaver, Martin J. Heslin, Selwyn M. Vickers, Thomas N. Wang, J. Bart Rose, Sushanth Reddy
Summary: The study on patients undergoing pancreatic resection at an academic institution revealed that most patients had insurance and hospital bill adjustments, resulting in the majority of patients not facing catastrophic health expenditure risk exceeding 10% of their estimated median household income.
AMERICAN JOURNAL OF SURGERY
(2021)
Review
Endocrinology & Metabolism
Rongzhi Wang, Rui Zheng-Pywell, H. Alexander Chen, James A. Bibb, Herbert Chen, J. Bart Rose
CLINICAL MEDICINE INSIGHTS-ENDOCRINOLOGY AND DIABETES
(2019)
Letter
Surgery
Steven M. Strasberg, J. Bart Rose
JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
(2018)